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MEDICAL POLICY – 8.01.22
Allogeneic Hematopoietic Stem Cell Transplantation for
Genetic Diseases and Acquired Anemias BCBSA Ref. Policy:
8.01.22
Effective Date: June 10, 2020
Last Revised: June 9, 2020
Replaces: 8.01.109
RELATED MEDICAL POLICIES:
7.01.50 Placental and Umbilical Cord Blood as a Source of Stem
Cells
8.01.15 Hematopoietic Cell Transplantation for Chronic
Lymphocytic Leukemia
and Small Lymphocytic Lymphoma
8.01.21 Allogeneic Hematopoietic Cell Transplantation for
Myelodysplastic
Syndromes and Myeloproliferative Neoplasms
8.01.24 Hematopoietic Cell Transplantation for Miscellaneous
Solid Tumors in
Adults
8.01.25 Hematopoietic Cell Transplantation for Autoimmune
Diseases
8.01.29 Hematopoietic Cell Transplantation for Hodgkin
Lymphoma
8.01.42 Hematopoietic Cell Transplantation for Primary
Amyloidosis
8.01.511 Hematopoietic Cell Transplantation for Solid Tumors of
Childhood
8.01.529 Hematopoietic Cell Transplantation for Non-Hodgkin
Lymphomas
8.01.532 Hematopoietic Cell Transplantation in the Treatment of
Germ-Cell
Tumors
Select a hyperlink below to be directed to that section.
POLICY CRITERIA | DOCUMENTATION REQUIREMENTS | CODING
RELATED INFORMATION | EVIDENCE REVIEW | REFERENCES | HISTORY
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above.
Introduction
Stem cells are like basic building blocks. They can develop into
different types of cells, including
cells that stimulate the production of new blood cells. This
policy describes when donor
(allogeneic) stem cells may be medically necessary for certain
anemias and genetic diseases.
Note: The Introduction section is for your general knowledge and
is not to be taken as policy coverage criteria. The
rest of the policy uses specific words and concepts familiar to
medical professionals. It is intended for
providers. A provider can be a person, such as a doctor, nurse,
psychologist, or dentist. A provider also can
be a place where medical care is given, like a hospital, clinic,
or lab. This policy informs them about when a
service may be covered.
https://www.premera.com/medicalpolicies-individual/7.01.50.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.15.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.15.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.21.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.21.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.24.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.24.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.25.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.29.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.42.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.511.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.529.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.532.pdfhttps://www.premera.com/medicalpolicies-individual/8.01.532.pdf
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Policy Coverage Criteria
Condition Medical Necessity Hemoglobinopathies Allogeneic
hematopoietic cell transplantation is considered
medically necessary for selected patients with
hemoglobinopathies:
• Sickle cell anemia for children or young adults with either
a
history of prior stroke or at increased risk of stroke or
end-
organ damage
• Homozygous -thalassemia (ie, thalassemia major)
Bone marrow failure
syndromes
Allogeneic hematopoietic cell transplantation is considered
medically necessary for selected patients with bone marrow
failure syndromes:
• Aplastic anemia including hereditary (including Fanconi
anemia,
dyskeratosis congenita, Shwachman-Diamond, Diamond-
Blackfan) or acquired (eg, secondary to drug or toxin
exposure)
forms
Primary
immunodeficiencies
Allogeneic hematopoietic cell transplantation is considered
medically necessary for selected patients with primary
immunodeficiencies:
• Absent or defective T cell function (eg, severe combined
immunodeficiency, Wiskott-Aldrich syndrome, X-linked
lymphoproliferative syndrome)
• Absent or defective natural killer function (eg,
Chédiak-Higashi
syndrome)
• Absent or defective neutrophil function (eg, Kostmann
syndrome, chronic granulomatous disease, leukocyte adhesion
defect)
The following lists the immunodeficiencies that have been
successfully treated by allogeneic hematopoietic cell
transplantation (allo-HCT) (Gennery & Cant et al, 2008).
• Lymphocyte Immunodeficiencies
o Adenosine deaminase deficiency
o Artemis deficiency
o Calcium channel deficiency
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Condition Medical Necessity o CD 40 ligand deficiency
o Cernunnos/X-linked lymphoproliferative disease deficiency
o CHARGE syndrome with immune deficiency
o Common gamma chain deficiency
o Deficiencies in CD45, CD3, CD8
o DiGeorge syndrome
o DNA ligase IV deficiency syndrome
o Interleukin-7 receptor alpha deficiency
o Janus-associated kinase 3 (JAK3) deficiency
o Major histocompatibility class II deficiency
o Omenn syndrome
o Purine nucleoside phosphorylase deficiency
o Recombinase-activating gene (RAG) 1/2 deficiency
o Reticular dysgenesis
o Winged helix deficiency
o Wiskott-Aldrich syndrome
o X-linked lymphoproliferative disease
o Zeta-chain-associated protein-70 (ZAP-70) deficiency
• Phagocytic Deficiencies
o Chédiak-Higashi syndrome
o Chronic granulomatous disease
o Griscelli syndrome, type 2
o Hemophagocytic lymphohistiocytosis
o Interferon-gamma receptor deficiencies
o Leukocyte adhesion deficiency
o Severe congenital neutropenias
o Shwachman-Diamond syndrome
• Other Immunodeficiencies
o Autoimmune lymphoproliferative syndrome
o Cartilage hair hypoplasia
o CD25 deficiency
o Hyper IgD and IgE syndromes
o Immunodeficiency, centromeric instability, and facial
dysmorphism (ICF) syndrome
o Immunodysregulation polyendocrinopathy enteropathy X-
linked (IPEX) syndrome
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Condition Medical Necessity o Nuclear factor-κ B (NF-κB)
essential modulator (NEMO)
deficiency
o NF-κB inhibitor, NF-κB-α deficiency
o Nijmegen breakage syndrome
Inherited metabolic disease Allogeneic hematopoietic cell
transplantation is considered
medically necessary for selected patients with the following
inherited metabolic diseases:
• Lysosomal and peroxisomal storage disorders except for
Hunter, Sanfilippo, and Morquio syndromes
o Allogeneic HCT has been proven effective in some cases
of:
▪ Hurler, Maroteaux-Lamy, and Sly syndromes
▪ Childhood onset cerebral X-linked
adrenoleukodystrophy
▪ Globoid-cell leukodystrophy
▪ Metachromatic leukodystrophy
▪ Alpha-mannosidosis
▪ Aspartylglucosaminuria
o Allogeneic HCT is possibly effective for:
▪ Fucosidosis
▪ Gaucher types 1 and 3
▪ Farber lipogranulomatosis
▪ Galactosialidosis
▪ GM1 gangliosidosis
▪ Mucolipidosis II (I-cell disease)
▪ Multiple sulfatase deficiency
▪ Niemann-Pick disease
▪ Neuronal ceroid lipofuscinosis
▪ Sialidosis
▪ Wolman disease
Allogeneic HCT is considered not medically necessary for
patients with the following inherited metabolic diseases:
• Hunter
• Sanfilippo
• Morquio transplantation syndromes (Mehta, 2004)
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Condition Medical Necessity Genetic disorders affecting
skeletal tissue
Allogeneic hematopoietic cell transplantation is considered
medically necessary for selected patients with genetic
disorders affecting skeletal tissue:
• Infantile malignant osteopetrosis (Albers-Schonberg disease
or
marble bone disease)
Condition Investigational Hemoglobinopathies Reduced-intensity
conditioning (RIC) and allogeneic HCT for
hemoglobinopathies is considered investigational.
Note: The experience with reduced-intensity conditioning and
allo-HCT for the diseases listed
in this policy has been limited to small numbers of patients and
has yielded mixed results,
depending on the disease category. In general, the results have
been most promising in the
bone marrow failure syndromes and primary immunodeficiencies. In
the hemoglobinopathies,
success has been hampered by difficulties with high rates of
graft rejection, and in adults, severe
graft-versus-host-disease. Phase 2/3 trials are ongoing or
completed examining the role of this
type of transplant for these diseases, as outlined in the
Ongoing and Unpublished Clinical
Trials section.
Documentation Requirements The patient’s medical records
submitted for review should document that medical necessity
criteria are met. The record should include clinical
documentation of:
• Diagnosis/condition
• History and physical examination documenting the severity of
the condition
Coding
Code Description
CPT 38230 Bone marrow harvesting for transplantation;
allogeneic
38232 Bone marrow harvesting for transplantation; autologous
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Code Description
38240 Hematopoietic progenitor cell (HPC); allogeneic
transplantation per donor
HCPCS
S2140 Cord blood harvesting for transplantation, allogeneic
S2142 Cord blood-derived stem-cell transplantation,
allogeneic
S2150 Bone marrow or blood-derived stem cells (peripheral or
umbilical), allogeneic or
autologous, harvesting, transplantation, and related
complications; including: pheresis
and cell preparation/storage; marrow ablative therapy; drugs,
supplies, hospitalization
with outpatient follow-up; medical/surgical, diagnostic,
emergency, and rehabilitative
services; and the number of days of pre and post transplant care
in the global
definition
Note: CPT codes, descriptions and materials are copyrighted by
the American Medical Association (AMA). HCPCS
codes, descriptions and materials are copyrighted by Centers for
Medicare Services (CMS).
Related Information
N/A
Evidence Review
Description
A number of inherited and acquired conditions have the potential
for severe and/or progressive
disease. For some conditions, allogeneic hematopoietic cell
transplantation (allo-HCT) has been
used to alter the natural history of the disease or potentially
offer a cure.
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Background
Genetic Diseases and Acquired Anemias
Hemoglobinopathies
Thalassemias result from variants in the globin genes, resulting
in reduced or absent
hemoglobin production, thereby reducing oxygen delivery. The
supportive treatment of -
thalassemia major requires life-long red blood cell transfusions
that lead to progressive iron
overload and the potential for organ damage and impaired
cardiac, hepatic, and endocrine
function. Sickle cell disease is caused by a single amino acid
substitution in the beta chain of
hemoglobin and, unlike thalassemia major, has a variable course
of clinical severity.1 Sickle cell
disease typically manifests clinically with anemia, severe
painful crises, acute chest syndrome,
stroke, chronic pulmonary and renal dysfunction, growth
retardation, neurologic deficits, and
premature death. The mean age of death for patients with sickle
cell disease has been
demonstrated as 42 years for males and 48 for females.
Treatment
The only definitive cure for thalassemia is to correct the
genetic defect with allogeneic HCT (allo-
HCT). Three major therapeutic options are available for sickle
cell disease: chronic blood
transfusions, hydroxyurea, and allo-HCT, the latter being the
only possibility for cure.1
Bone Marrow Failure Syndromes
Aplastic anemia in children is rare; most often, it is
idiopathic and, less commonly, due to a
hereditary disorder. Inherited syndromes include Fanconi anemia,
a rare, autosomal recessive
disease characterized by genomic instability, with congenital
abnormalities, chromosome
breakage, cancer susceptibility, and progressive bone marrow
failure leading to pancytopenia
and severe aplastic anemia. Frequently this disease terminates
in a myelodysplastic syndrome or
acute myelogenous leukemia. Most patients with Fanconi anemia
succumb to the complications
of severe aplastic anemia, leukemia, or solid tumors, with a
median survival of 30 years of age.2
Dyskeratosis congenita is characterized by marked telomere
dysregulation with clinical features
of reticulated skin hyperpigmentation, nail dystrophy, and oral
leukoplakia.3 Early mortality is
associated with bone marrow failure, infections, pulmonary
complications, or malignancy.
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Variants affecting ribosome assembly and function are associated
with Shwachman-Diamond
syndrome, and Diamond-Blackfan syndrome.3 Shwachman-Diamond has
clinical features that
include pancreatic exocrine insufficiency, skeletal
abnormalities, and cytopenias, with some
patients developing aplastic anemia. As with other bone marrow
failure syndromes, patients are
at increased risk of myelodysplastic syndrome and malignant
transformation, especially acute
myelogenous leukemia. Diamond-Blackfan anemia is characterized
by absent or decreased
erythroid precursors in the bone marrow, with 30% of patients
also having a variety of physical
anomalies.3
Treatment
In Fanconi anemia, allo-HCT is currently the only treatment that
definitively restores normal
hematopoiesis. Excellent results have been observed with the use
of human leukocyte antigen
(HLA)-matched sibling allo-HCT, with cure of the marrow failure
and amelioration of the risk of
leukemia.
Primary Immunodeficiencies
The primary immunodeficiencies are a genetically heterogeneous
group of diseases that affect
distinct components of the immune system. More than 120 gene
defects have been described,
causing more than 150 disease phenotypes.4 The most severe
defects (collectively known as
severe combined immunodeficiency [SCID]) cause an absence or
dysfunction of T lymphocytes
and sometimes B lymphocytes and natural killer cells.4
Treatment
Without treatment, patients with SCID usually die by 12 to 18
months of age. With supportive
care, including prophylactic medication, the lifespan of these
patients can be prolonged, but
long-term outlook is still poor, with many dying from infectious
or inflammatory complications
or malignancy by early adulthood.4 Allogeneic bone marrow
transplantation is the only definitive
cure at this time, and the treatment of choice for SCID and
other primary immunodeficiencies,
including Wiskott-Aldrich syndrome and congenital defects of
neutrophil function.5
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Inherited Metabolic Diseases
Lysosomal storage disorders consist of many different rare
diseases caused by a single gene
defect, and most are inherited as an autosomal recessive trait.6
Lysosomal storage disorders are
caused by specific enzyme deficiencies that result in defective
lysosomal acid hydrolysis of
endogenous macromolecules that subsequently accumulate as a
toxic substance. Peroxisomal
storage disorders arise due to a defect in a membrane
transporter protein that leads to defects
in the metabolism of long-chain fatty acids. Lysosomal storage
disorders and peroxisomal
storage disorders affect multiple organ systems, including the
central and peripheral nervous
systems. These disorders are progressive and often fatal in
childhood due to both the
accumulation of toxic substrate and a deficiency of the product
of the enzyme reaction.6 Hurler
syndrome usually leads to premature death by 5 years of age.
Treatment
Exogenous enzyme replacement therapy is available for a limited
number of the inherited
metabolic diseases; however, these drugs don’t cross the
blood-brain barrier, which results in
ineffective treatment of the central nervous system. Stem cell
transplantation provides a
constant source of enzyme replacement from the engrafted donor
cells, which are not impeded
by the blood-brain barrier.6 The donor-derived cells can migrate
and engraft in many organ
systems, giving rise to different types of cells (eg, microglial
cells in the brain and Kupffer cells in
the liver).6
Allogeneic HCT has been primarily used to treat the inherited
metabolic diseases that belong to
the lysosomal and peroxisomal storage disorders, as listed in
the Table 1.6 The first stem cell
transplant for an inherited metabolic disease was performed in
1980 in a patient with Hurler
syndrome. Since that time, more than 1,000 transplants have been
performed worldwide.6
Table 1. Lysosomal and Peroxisomal Storage Disorders
Category Diagnosis Other Names
Mucopolysaccharidosis (MPS) MPS I H or H/S
MPS II
MPS III A-D
MPS IV A-B
Hurler syndrome or Hurler-Scheie,
syndrome
Hunter syndrome
Sanfilippo syndrome A-D
Morquio syndrome A-B
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Category Diagnosis Other Names
MPS VI
MPS VII
Maroteaux-Lamy syndrome
Sly sundrome
Sphingolipidosis Fabry disease
Farber disease
Gaucher disease types 1 and 3
GM1 gangliosidosis
Niemann-Pick disease A and B
Tay-Sachs disease
Sandhoff disease
Globoid leukodystrophy
Metachromatic leukodystrophy
Lipogranuomatosis
Krabbe disease
MLD
Glycoproteinosis Aspartylglucosaminuria
Fucosidosis
Alpha-Mannosidosis
Beta-Mannosidosis
Mucolipidosis III and IV
Sialidosis
Other lipidoses Niemann-Pick disease C
Wolman disease
Ceroid lipofuscinosis
Batten disease
Glycogen storage Glycogen storage disease type II Pompe
disease
Multiple enzyme deficiency Galactosialidosis
Mucolipidosis type II
I-cell disease
Lysosomal transport defects Cystinosis
Sialic acid storage disease
Salla disease
Peroxisomal storage disorders Adrenoleukodystrophy
Adrenomyeloneuropathy
ALD
AMN
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Genetic Disorders Affecting Skeletal Tissue
Osteopetrosis is a condition caused by defects in osteoclast
development and/or function. The
osteoclast (the cell that functions in the breakdown and
resorption of bone tissue) is known to
be part of the hematopoietic family and shares a common
progenitor with the macrophage in
the bone marrow.7 Osteopetrosis is a heterogeneous group of
heritable disorders, resulting in
several different types of variable severity. The most severely
affected patients are those with
infantile malignant osteopetrosis (Albers-Schonberg disease or
marble bone disease). Patients
with infantile malignant osteopetrosis suffer from dense bone,
including a heavy head with
frontal bossing, exophthalmos, blindness by approximately 6
months of age, and severe
hematologic malfunction with bone marrow failure.7 Seventy
percent of these patients die
before the age of 6 years, often of recurrent infections.7
Treatment
HCT is the only curative therapy for this fatal disease.
Hematopoietic Cell Transplantation
Hematopoietic cell transplantation (HCT) is a procedure in which
hematopoietic stem cells are
infused to restore bone marrow function in patients who receive
bone-marrow-toxic doses of
cytotoxic drugs with or without whole body radiotherapy.
Hematopoietic stem cells may be
obtained from the transplant recipient (autologous HCT) or a
donor (allo-HCT). They can be
harvested from bone marrow, peripheral blood, or umbilical cord
blood and placenta shortly
after delivery of neonates. Cord blood is addressed in a
separate policy (see Related Policies).
Immunologic compatibility between infused hematopoietic stem
cells and the recipient is not an
issue in autologous HCT. In allogeneic stem cell
transplantation, immunologic compatibility
between donor and patient is a critical factor for achieving a
successful outcome. Compatibility
is established by typing ofHLA using cellular, serologic, or
molecular techniques. HLA refers to
the gene complex expressed at the HLA-A, -B, and -DR (antigen-D
related) loci on each arm of
chromosome 6. An acceptable donor will match the patient at all
or most of the HLA loci.
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Conditioning for Hematopoietic Cell Transplantation
Conventional Conditioning
The conventional practice of allo-HCT involves administration of
cytotoxic agents (eg,
cyclophosphamide, busulfan) with or without total body
irradiation at doses sufficient to cause
bone marrow ablation in the recipient. The beneficial treatment
effect of this procedure is due to
a combination of the initial eradication of malignant cells and
subsequent graft-versus-
malignancy effect mediated by non-self-immunologic effector
cells. While the slower graft-
versus-malignancy effect is considered the potentially curative
component, it may be
overwhelmed by existing disease in the absence of pretransplant
conditioning. Intense
conditioning regimens are limited to patients who are
sufficiently medically fit to tolerate
substantial adverse effects. These include opportunistic
infections secondary to loss of
endogenous bone marrow function and organ damage or failure
caused by cytotoxic drugs.
Subsequent to graft infusion in allo-HCT, immunosuppressant
drugs are required to minimize
graft rejection and graft-versus-host disease, which increases
susceptibility to opportunistic
infections.
The success of autologous HCT is predicated on the potential of
cytotoxic chemotherapy, with
or without radiotherapy, to eradicate cancerous cells from the
blood and bone marrow. This
permits subsequent engraftment and repopulation of the bone
marrow with presumably normal
hematopoietic stem cells obtained from the patient before
undergoing bone marrow ablation.
Therefore, autologous HCT is typically performed as
consolidation therapy when the patient’s
disease is in complete remission. Patients who undergo
autologous HCT are also susceptible to
chemotherapy-related toxicities and opportunistic infections
before engraftment, but not GVH
disease.
Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell
Transplantation
RIC refers to the pretransplant use of lower doses of cytotoxic
drugs or less intense regimens of
radiotherapy than are used in traditional full-dose
myeloablative conditioning treatments.
Although the definition of RIC is variable, with numerous
versions employed, all regimens seek
to balance the competing effects of relapse due to residual
disease and non-relapse mortality.
The goal of RIC is to reduce disease burden and to minimize
associated treatment-related
morbidity and non-relapse mortality in the period during which
the beneficial graft-versus-
malignancy effect of allogeneic transplantation develops. RIC
regimens range from nearly total
myeloablative to minimally myeloablative with lymphoablation,
with intensity tailored to specific
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diseases and patient condition. Patients who undergo RIC with
allo-HCT initially demonstrate
donor cell engraftment and bone marrow mixed chimerism. Most
will subsequently convert to
full-donor chimerism. In this review, the term reduced-intensity
conditioning will refer to all
conditioning regimens intended to be nonmyeloablative.
Summary of Evidence
For individuals who have a hemoglobinopathy, bone marrow failure
syndrome, primary
immunodeficiency, inherited metabolic syndrome disease
(specifically those other than Hunter,
Sanfilippo, or Morquio syndromes), or a genetic disorder
affecting skeletal tissue who receive
allo-HCT, the evidence includes mostly case series, case
reports, and registry data. The relevant
outcomes are overall survival, disease-specific survival,
quality of life, and treatment-related
morbidity. The evidence has shown that, for most of these
disorders, there is a demonstrable
improvement in overall survival and other disease-specific
outcomes. Allo-HCT is likely to
improve health outcomes in select patients with certain
inherited and acquired diseases. The
evidence is sufficient to determine that the technology results
in a meaningful improvement in
the net health outcome.
For individuals who have an inherited metabolic syndrome disease
(specifically those including
Hunter, Sanfilippo, and Morquio syndromes) who receive allo-HCT,
the evidence includes case
reports. The relevant outcomes are overall survival,
disease-specific survival, symptoms, quality
of life, and treatment-related morbidity. Use of allo-HCT to
treat patients with Hunter,
Sanfilippo, or Morquio syndromes does not result in improvements
in neurologic,
neuropsychologic, and neurophysiologic function. The evidence is
insufficient to determine the
effects of the technology on health outcomes.
Ongoing and Unpublished Clinical Trials
Some currently unpublished trials that might influence this
review are listed in Table 2.
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Table 2. Summary of Key Trials
NCT No. Trial Name Planned
Enrollment
Completion
Date
Ongoing
NCT00176852 Allogeneic Hematopoietic Stem Cell Transplant
for
Patients With High Risk Hemoglobinopathy Using a
Preparative Regimen to Achieve Stable Mixed Chimerism
22 Jan 2020
NCT00358657 HLA-Haploidentical Related Marrow Grafts for the
Treatment of Primary Immunodeficiencies and Other
Nonmalignant Disorders Using Conditioning With Low-
Dose Cyclophosphamide, TBI and Fludarabine and
Postgrafting Cyclophosphamide
20 Dec 2023
NCT02356653 Expanded Access Protocol Using CD3+/CD19+
Depleted
Unrelated Donor or Partially Matched Related Donor
Peripheral Stem Cells
100 Jan 2020
NCT02986698 A Single-Center, Non-Randomized Study of the
Safety
and Efficacy of In Utero Hematopoietic Stem Cell
Transplantation for the Treatment of Fetuses With Alpha
Thalassemia Major
10 Feb 2024
Unpublished
NCT00176826 In-vivo T-cell Depletion and Hematopoietic Stem
Cell
Transplantation for Life-Threatening Immune Deficiencies
and Histiocytic Disorders
22 Aug 2015
(Terminated)
NCT00775931 Allogeneic Hematopoietic Stem Cell Transplantation
For
Severe Osteopetrosis
23 Jun 2013
(completed)
NCT00553098 Hematopoietic Cell Transplantation for Treatment
of
Patients With Primary Immunodeficiencies and Other
Nonmalignant Inherited Disorders Using Low-Dose TBI
and Fludarabine With or Without Campath®
25 Mar 2015
NCT: national clinical trial.
Clinical Input Received from Physician Specialty Societies and
Academic
Medical Centers
While the various physician specialty societies and academic
medical centers may collaborate
with and make recommendations during this process, through the
provision of appropriate
https://www.clinicaltrials.gov/ct2/show/NCT00176852?term=NCT00176852&rank=1https://www.clinicaltrials.gov/ct2/show/NCT00358657?term=NCT00358657&rank=1https://www.clinicaltrials.gov/ct2/show/NCT02356653?term=Processing+of+stem+cells+using+the+CliniMACs+device+to+selectively+deplete+specific+T+cells+to+decrease+risk+of+graft+versus+host+disease+when+using+donor+stem+cells+which+are+not+fully+matched&rank=1https://www.clinicaltrials.gov/ct2/show/NCT02986698?term=NCT02986698&rank=1https://www.clinicaltrials.gov/ct2/show/NCT00176826?term=NCT00176826&rank=1https://www.clinicaltrials.gov/ct2/show/NCT00775931?term=NCT00775931&rank=1https://www.clinicaltrials.gov/ct2/show/NCT00553098?term=NCT00553098&rank=1
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reviewers, input received does not represent an endorsement or
position statement by the
physician specialty societies or academic medical centers,
unless otherwise noted.
In response to requests, input was received from 1 physician
specialty society (3 reviewers) and 3
academic medical centers while this policy was under review in
2009. There was general
agreement with the policy statements. In particular, the
reviewers were specifically asked to
comment on the use of hematopoietic cell transplant in the
inherited metabolic diseases, except
for Hunter, Sanfilippo, and Morquio syndromes; 4 reviewers
agreed with the current policy
statement, 1 disagreed, and 1 did not address this specific
question.
Practice Guidelines and Position Statements
American Society for Blood and Marrow Transplantation
The American Society for Blood and Marrow Transplantation (2015)
published consensus
guidelines on the use of hematopoietic cell transplantation
(HCT) to treat specific conditions in
and out of the clinical trial settings.57 Specific to this
review Table 3 provides the allogeneic
guidelines for specific indications.
Table 3. Recommendations for Use of Allogeneic HCT to Treat
Genetic
Diseases and Acquired Anemias
Indications Allo-HCT
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Indications Allo-HCT 18 Years
Severe aplastic anemia, new diagnosis S
Severe aplastic anemia, relapse/refractory S
Fanconi anemia R
Dyskeratosis congenita R
Sickle cell disease C
Thalassemia D
Hemophagocytic syndromes, refractory R
Mast cell diseases R
Common variable immunodeficiency R
Wiskott-Aldrich syndrome R
Chronic granulomatous disease R
Multiple sclerosis N
Systemic sclerosis N
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Indications Allo-HCT >18 Years
Rheumatoid arthritis N
Systemic lupus erythematosus N
Crohn’s disease N
Polymyositis-dermatomyositis N
C: clinical evidence available; D: developmental; HCT:
hematopoietic cell transplantation; N: not generally
recommended; R: standard of care, rare indication; S: standard
of care.
British Committee for Standards in Haematology
The British Committee for Standards in Haematology (2015)
published guidelines on the
diagnosis and management of adult aplastic anemia.58 The
following key recommendations on
HCT were included in the guidelines:
• Matched sibling donor (allogeneic) HCT is the treatment of
choice for severe aplastic
anemia; however, for patients aged 35 to 50 years, patients need
to be assessed for
comorbidities before being considered for HCT.
• For adults, unrelated donor HCT should be considered if
patients fail to respond to a single
course of immunosuppressive therapy.
• Although there have been improvements in outcomes after
alternative donor HCT, these
transplants are still experimental, and expert consultation
should be sought before
considering their use.
European Blood and Marrow Transplantation
The European Blood and Marrow Transplantation (2014) provided
consensus-based
recommendations on indications for HCT and transplant management
in the
hemoglobinopathies.10
Pediatric Haemato-Oncology Italian Association
The Pediatric Haemato-Oncology Italian Association (2015) issued
guidelines on the diagnosis
and treatment of acquired aplastic anemia in childhood.59
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Page | 18 of 24 ∞
Medicare National Coverage
There is no national coverage determination.
Regulatory Status
The U.S. Food and Drug Administration regulates human cells and
tissues intended for
implantation, transplantation, or infusion through the Center
for Biologics Evaluation and
Research, under the Code of Federal Regulation title 21, parts
1270 and 1271. Hematopoietic
stem cells are included in these regulations.
References
1. Bhatia M, Walters MC. Hematopoietic cell transplantation for
thalassemia and sickle cell disease: past, present and future.
Bone
Marrow Transplant. Jan 2008;41(2):109-117. PMID 18059330
2. Mehta P. Hematopoietic stem cell transplantation for
inherited bone marrow failure syndromes. In: Mehta P, ed. Pediatric
Stem
Cell Transplantation. Sudbury, MA: Jones and Bartlett;
2004:281-316.
3. Gluckman E, Wagner JE. Hematopoietic stem cell
transplantation in childhood inherited bone marrow failure
syndrome. Bone
Marrow Transplant. Jan 2008;41(2):127-132. PMID 18084332
4. Gennery AR, Cant AJ. Advances in hematopoietic stem cell
transplantation for primary immunodeficiency. Immunol Allergy
Clin
North Am. May 2008;28(2):439-456, x-xi. PMID 18424341
5. Porta F, Forino C, De Martiis D, et al. Stem cell
transplantation for primary immunodeficiencies. Bone Marrow
Transplant. Jun
2008;41(Suppl 2):S83-86. PMID 18545252
6. Prasad VK, Kurtzberg J. Emerging trends in transplantation of
inherited metabolic diseases. Bone Marrow Transplant. Jan
2008;41(2):99-108. PMID 18176609
7. Askmyr MK, Fasth A, Richter J. Towards a better understanding
and new therapeutics of osteopetrosis. Br J Haematol. Mar
2008;140(6):597-609. PMID 18241253
8. MacMillan ML, Walters MC, Gluckman E. Transplant outcomes in
bone marrow failure syndromes and hemoglobinopathies.
Semin Hematol. Jan 2010;47(1):37-45. PMID 20109610
9. Smiers FJ, Krishnamurti L, Lucarelli G. Hematopoietic stem
cell transplantation for hemoglobinopathies: current practice
and
emerging trends. Pediatr Clin North Am. Feb 2010;57(1):181-205.
PMID 20307718
10. Angelucci E, Matthes-Martin S, Baronciani D, et al.
Hematopoietic stem cell transplantation in thalassemia major and
sickle cell
disease: indications and management recommendations from an
international expert panel. Haematologica. May
2014;99(5):811-820. PMID 24790059
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11. Mathews V, Srivastava A, Chandy M. Allogeneic stem cell
transplantation for thalassemia major. Hematol Oncol Clin North
Am.
Dec 2014;28(6):1187-1200. PMID 25459187
12. Locatelli F, Kabbara N, Ruggeri A, et al. Outcome of
patients with hemoglobinopathies given either cord blood or bone
marrow
transplantation from an HLA-identical sibling. Blood. Aug 08
2013;122(6):1072-1078. PMID 23692854
13. Mehta P. Hematopoietic stem cell transplantation for
hemoglobinopathies. In: Mehta P, ed. Pediatric Stem Cell
Transplantation.
Sudbury, MA: Jones and Bartlett; 2004:259-279.
14. Mahmoud HK, Elhaddad AM, Fahmy OA, et al. Allogeneic
hematopoietic stem cell transplantation for non- malignant
hematological disorders. J Adv Res. May 2015;6(3):449-458. PMID
26257943
15. Bernardo ME, Piras E, Vacca A, et al. Allogeneic
hematopoietic stem cell transplantation in thalassemia major:
results of a
reduced-toxicity conditioning regimen based on the use of
treosulfan. Blood. Jul 12 2012;120(2):473- 476. PMID 22645178
16. Anurathapan U, Pakakasama S, Mekjaruskul P, et al. Outcomes
of thalassemia patients undergoing hematopoietic stem cell
transplantation by using a standard myeloablative versus a novel
reduced-toxicity conditioning regimen according to a new risk
stratification. Biol Blood Marrow Transplant. Dec
2014;20(12):2066- 2071. PMID 25064743
17. Oringanje C, Nemecek E, Oniyangi O. Hematopoietic stem cell
transplantation for people with sickle cell disease. Cochrane
Database Syst Rev. May 31 2013(5):CD007001. PMID 23728664
18. Oringanje C, Nemecek E, Oniyangi O. Hematopoietic stem cell
transplantation for people with sickle cell disease. Cochrane
Database Syst Rev. May 19 2016(5):CD007001. PMID 27194464
19. Bernaudin F, Socie G, Kuentz M, et al. Long-term results of
related myeloablative stem-cell transplantation to cure sickle
cell
disease. Blood. Oct 1 2007;110(7):2749-2756. PMID 17606762
20. Walters MC, Patience M, Leisenring W, et al. Bone marrow
transplantation for sickle cell disease. N Engl J Med. Aug 8
1996;335(6):369-376. PMID 8663884
21. Walters MC, Storb R, Patience M, et al. Impact of bone
marrow transplantation for symptomatic sickle cell disease: an
interim
report. Multicenter investigation of bone marrow transplantation
for sickle cell disease. Blood. Mar 15 2000;95(6):1918-1924.
PMID 10706855
22. Hsieh MM, Fitzhugh CD, Weitzel RP, et al. Nonmyeloablative
HLA-matched sibling allogeneic hematopoietic stem cell
transplantation for severe sickle cell phenotype. JAMA. Jul 02
2014;312(1):48-56. PMID 25058217
23. Mehta P, Locatelli F, Stary J, et al. Bone marrow
transplantation for inherited bone marrow failure syndromes.
Pediatr Clin North
Am. Feb 2010;57(1):147-170. PMID 20307716
24. Miano M, Dufour C. The diagnosis and treatment of aplastic
anemia: a review. Int J Hematol. Jun 2015;101(6):527-535. PMID
25837779
25. Bacigalupo A. Bone marrow transplantation for acquired
severe aplastic anemia. Hematol Oncol Clin North Am. Dec
2014;28(6):1145-1155. PMID 25459184
26. Dufour C, Svahn J. Fanconi anaemia: new strategies. Bone
Marrow Transplant. Jun 2008;41(Suppl 2):S90-95. PMID 18545254
27. Zanis-Neto J, Flowers ME, Medeiros CR, et al. Low-dose
cyclophosphamide conditioning for haematopoietic cell
transplantation
from HLA-matched related donors in patients with Fanconi
anaemia. Br J Haematol. Jul 2005;130(1):99-106. PMID 15982351
28. Wagner JE, Eapen M, MacMillan ML, et al. Unrelated donor
bone marrow transplantation for the treatment of Fanconi
anemia.
Blood. Mar 1 2007;109(5):2256-2262. PMID 17038525
29. Gadalla SM, Sales-Bonfim C, Carreras J, et al. Outcomes of
allogeneic hematopoietic cell transplantation in patients with
dyskeratosis congenita. Biol Blood Marrow Transplant. Aug
2013;19(8):1238-1243. PMID 23751955
30. Cesaro S, Oneto R, Messina C, et al. Haematopoietic stem
cell transplantation for Shwachman-Diamond disease: a study
from
the European Group for blood and marrow transplantation. Br J
Haematol. Oct 2005;131(2):231-236. PMID 16197455
31. Roy V, Perez WS, Eapen M, et al. Bone marrow transplantation
for Diamond-Blackfan anemia. Biol Blood Marrow Transplant.
Aug 2005;11(8):600-608. PMID 16041310
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Page | 20 of 24 ∞
32. Kim H, Lee JH, Joo YD, et al. A randomized comparison of
cyclophosphamide vs. reduced dose cyclophosphamide plus
fludarabine for allogeneic hematopoietic cell transplantation in
patients with aplastic anemia and hypoplastic myelodysplastic
syndrome. Ann Hematol. Sep 2012;91(9):1459-1469. PMID
22526363
33. Dufour C, Pillon M, Socie G, et al. Outcome of aplastic
anaemia in children. A study by the severe aplastic anaemia and
paediatric disease working parties of the European group blood
and bone marrow transplant. Br J Haematol. May
2015;169(4):565-573. PMID 25683884
34. Smith AR, Gross TG, Baker KS. Transplant outcomes for
primary immunodeficiency disease. Semin Hematol. Jan
2010;47(1):79-
85. PMID 20109615
35. Szabolcs P, Cavazzana-Calvo M, Fischer A, et al. Bone marrow
transplantation for primary immunodeficiency diseases. Pediatr
Clin North Am. Feb 2010;57(1):207-237. PMID 20307719
36. Ahlin A, Fugelang J, de Boer M, et al. Chronic granulomatous
disease-haematopoietic stem cell transplantation versus
conventional treatment. Acta Paediatr. Nov
2013;102(11):1087-1094. PMID 23937637
37. Gungor T, Teira P, Slatter M, et al. Reduced-intensity
conditioning and HLA-matched haemopoietic stem-cell transplantation
in
patients with chronic granulomatous disease: a prospective
multicentre study. Lancet. Feb 01 2014;383(9915):436-448. PMID
24161820
38. Filipovich A. Hematopoietic cell transplantation for
correction of primary immunodeficiencies. Bone Marrow Transplant.
Aug
2008;42(Suppl 1):S49-S52. PMID 18724301
39. Hassan A, Booth C, Brightwell A, et al. Outcome of
hematopoietic stem cell transplantation for adenosine
deaminase-deficient
severe combined immunodeficiency. Blood. Oct 25
2012;120(17):3615-3624; quiz 3626. PMID 22791287
40. Filipovich AH, Stone JV, Tomany SC, et al. Impact of donor
type on outcome of bone marrow transplantation for Wiskott-
Aldrich syndrome: collaborative study of the International Bone
Marrow Transplant Registry and the National Marrow Donor
Program. Blood. Mar 15 2001;97(6):1598-1603. PMID 11238097
41. Moratto D, Giliani S, Bonfim C, et al. Long-term outcome and
lineage-specific chimerism in 194 patients with Wiskott-Aldrich
syndrome treated by hematopoietic cell transplantation in the
period 1980-2009: an international collaborative study. Blood.
Aug 11 2011;118(6):1675-1684. PMID 21659547
42. Marsh RA, Bleesing JJ, Chandrakasan S, et al.
Reduced-intensity conditioning hematopoietic cell transplantation
is an effective
treatment for patients with SLAM-associated protein
deficiency/X-linked lymphoproliferative disease type 1. Biol Blood
Marrow
Transplant. Oct 2014;20(10):1641-1645. PMID 24923536
43. Mehta P. Metabolic diseases. In: Mehta P, ed. Pediatric Stem
Cell Transplantation. Sudbury, MA: Jones and Bartlett;
2004:233-
258.
44. Guffon N, Bertrand Y, Forest I, et al. Bone marrow
transplantation in children with Hunter syndrome: outcome after 7
to 17
years. J Pediatr. May 2009;154(5):733-737. PMID 19167723
45. Vellodi A, Young E, New M, et al. Bone marrow
transplantation for Sanfilippo disease type B. J Inherit Metab
Dis.
1992;15(6):911-918. PMID 1293388
46. Bordigoni P, Vidailbet M, Lena M, et al. Bone marrow
transplantation for Sanfilippo syndrome. In: Hobbs JR, ed.
Correction of
Certain Genetic Diseases by Transplantation. London: Cogent;
1989:114-119.
47. Boelens JJ, Prasad VK, Tolar J, et al. Current international
perspectives on hematopoietic stem cell transplantation for
inherited
metabolic disorders. Pediatr Clin North Am. Feb
2010;57(1):123-145. PMID 20307715
48. Prasad VK, Kurtzberg J. Transplant outcomes in
mucopolysaccharidoses. Semin Hematol. Jan 2010;47(1):59- 69. PMID
20109613
49. Rovelli AM. The controversial and changing role of
haematopoietic cell transplantation for lysosomal storage
disorders: an
update. Bone Marrow Transplant. Jun 2008;41(Suppl 2):S87-89.
PMID 18545253
50. Aldenhoven M, Wynn RF, Orchard PJ, et al. Long-term outcome
of Hurler syndrome patients after hematopoietic cell
transplantation: an international multicenter study. Blood. Mar
26 2015;125(13):2164-2172. PMID 25624320
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Page | 21 of 24 ∞
51. Boelens JJ, Wynn RF, O'Meara A, et al. Outcomes of
hematopoietic stem cell transplantation for Hurler's syndrome in
Europe: a
risk factor analysis for graft failure. Bone Marrow Transplant.
Aug 2007;40(3):225-233. PMID 17529997
52. Hansen MD, Filipovich AH, Davies SM, et al. Allogeneic
hematopoietic cell transplantation (HCT) in Hurler's syndrome using
a
reduced intensity preparative regimen. Bone Marrow Transplant.
Feb 2008;41(4):349-353. PMID 18026148
53. Mynarek M, Tolar J, Albert MH, et al. Allogeneic
hematopoietic SCT for alpha-mannosidosis: an analysis of 17
patients. Bone
Marrow Transplant. Mar 2012;47(3):352-359. PMID 21552297
54. Miller WP, Rothman SM, Nascene D, et al. Outcomes after
allogeneic hematopoietic cell transplantation for childhood
cerebral
adrenoleukodystrophy: the largest single-institution cohort
report. Blood. Aug 18 2011;118(7):1971-1978. PMID 21586746
55. Steward CG. Hematopoietic stem cell transplantation for
osteopetrosis. Pediatr Clin North Am. Feb 2010;57(1):171-180.
PMID
20307717
56. Driessen GJ, Gerritsen EJ, Fischer A, et al. Long-term
outcome of haematopoietic stem cell transplantation in
autosomal
recessive osteopetrosis: an EBMT report. Bone Marrow Transplant.
Oct 2003;32(7):657-663. PMID 13130312
57. Majhail NS, Farnia SH, Carpenter PA, et al. Indications for
autologous and allogeneic hematopoietic cell transplantation:
guidelines from the American Society for Blood and Marrow
Transplantation. Biol Blood Marrow Transplant. Nov
2015;21(11):1863-1869. PMID 26256941
58. Killick SB, Bown N, Cavenagh J, et al. Guidelines for the
diagnosis and management of adult aplastic anaemia. Br J
Haematol.
Jan 2016;172(2):187-207. PMID 26568159
59. Barone A, Lucarelli A, Onofrillo D, et al. Diagnosis and
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2015;55(1):40-47. PMID 25976466
History
Date Comments 02/01/00 Add to Therapy Section - New policy.
Policy represents revision of original 7.03.10.
Myelofibrosis and myelodysplasia, originally included in that
policy, are now addressed
in policy CP.MP.BC.8.01.21. Policy replaced CP.MP.BC.8.01.22,
with policy statement on
remaining indications unchanged.
11/12/02 Replace policy - Policy reviewed without literature
review; new review date only.
Replaces CP.MP.PR.8.01.109.
12/10/02 Replace policy - Policy reviewed by OAP; no criteria
changes.
05/13/03 Replace policy - Update CPT codes only.
07/13/04 Replace policy - Policy reviewed; no change to policy
statement.
07/12/05 Replace policy - Policy reviewed with literature
search; no change to policy statement.
No further review scheduled; status changed from BC to AR.
06/09/06 Update Scope and Disclaimer - No other changes.
-
Page | 22 of 24 ∞
Date Comments 03/13/07 Replace policy - Policy updated with
literature search; no change in policy statement.
Policy status updated to annual review with literature search
(AR to BC). Reviewed and
recommended by OAP on February 22, 2007.
10/09/07 Cross References Updated - No other changes.
11/12/07 Code updated - CPT code 86817 deleted as directed by
RPIW.
04/08/08 Replace policy - Policy updated with literature search;
no change to the policy
statement. Reviewed and recommended by OAP on February 21,
2008.
05/13/08 Cross Reference Update - No other changes
12/08/09 Replace policy - Policy updated and extensively edited
based on literature search.
Except for one change, the intent of the policy statements is
unchanged. The change in
the policy statement is that treatment of Hunter, Sanfilippo,
and Morquio syndromes
are not included in the list of lysosomal and peroxisomal
storage diseases where allo-
HSCT may be considered medically necessary and are now
considered not medically
necessary. References added. On hold for notification, release
to publish on May 10,
2010.
12/14/10 Replace policy - Policy updated and extensively edited
with information on use of
reduced-intensity conditioning based upon literature search.
References 9, 10, 15, 18,
19, 21, 22, 25, 26, 30 and 33 have been added; the policy
statements remain
unchanged. Reviewed and approved by OAP on November 18,
2010.
10/11/11 Replace policy – Policy updated with literature search;
reference 30 added; no change
in policy statement. HCPCS and ICD-9 diagnosis codes updated;
ICD-10 codes added.
Codes 38220 and 38221 removed.
01/24/12 Code 38232 added.
02/09/12 The CPT codes 38204 and 38206 removed from the policy;
they do not apply.
06/20/12 Minor update: Related Policies updated; 8.01.17
replaced 8.01.507 effective June 12,
2012.
08/01/12 Update to Related Policies Titles: 8.01.17, 8.01.20,
8.01.21, 8.01.29, 8.01.30, 8.01.31,
8.01.35, and 8.01.520.
11/27/12 Replace policy - Policy updated with literature search;
references 15, 25 and 27 added;
no change in policy statements. HCPCS codes G0265 – G0267
removed as these are
deleted codes as of 2008.
02/01/13 Update Related Policies, change title of policy
8.01.21.
03/20/13 The following codes were removed from the policy, as
they were not suspending and
just informational: HCPCS J9000-J9999 and Q0083 – Q0085.
09/30/13 Update Related Policies. Change title to 8.01.31.
-
Page | 23 of 24 ∞
Date Comments 12/04/13 Replace policy. Rationale updated based
on a literature search through July 15, 2013;
references 16 and 23 added; others renumbered/removed. Removed
CPT 38231-code
deleted in 2003. Policy statements unchanged.
02/27/14 Update Related Policies. Change title to 8.01.30.
03/11/14 Coding Update. Codes 41.02, 41.03, and 41.05 were
removed per ICD-10 mapping
project; these codes are not utilized for adjudication of
policy.
03/21/14 Update Related Policies. Add 8.01.15 and delete
8.01.514.
04/18/14 Update Related Policies. Remove 8.01.20 and add
8.01.529.
06/24/14 Update Related Policies. Delete 8.01.35 and 8.01.42 and
add 8.01.530 and 8.01.532
11/10/14 Annual Review. Policy updated with literature review
through July 31, 2014; references
15, 17, 23, 29-30, and 35 added; no change in policy statements.
ICD-9 and ICD-10
diagnosis and procedure codes removed; they do not relate to
adjudication.
02/03/15 Update Related Policies. Remove 8.01.23, 8.01.28 and
8.01.30.
11/10/15 Annual Review. Policy updated with literature search;
reference 48 added; no change in
policy statement.
05/01/16 Annual Review, approved April 12, 2016. Policy updated
with literature review through
October 27, 2015; references 11-13, 15, 24-25, 33, 46, and 57
added. Policy statements
unchanged.
08/09/16 Update Related Policies. Remove 8.01.27 as it was
archived.
09/30/16 Coding Update. Remove CPT 86817 from coding
section.
11/04/16 Coding update. Removed codes that are transplant
benefit related.
04/01/17 Update Related Policies; updated some of the titles.
Minor formatting update.
08/01/17 Updated title of Related Policy 8.01.511.
12/01/17 Annual Review, approved November 9, 2017. Policy
statements reorganized for clarity,
intent remains unchanged.
05/01/18 Annual Review, approved April 3, 2018. Policy updated
with literature review through
November 2017; reference 57 added. Policy statement
unchanged.
04/01/19 Annual Review, approved March 5, 2019. Policy updated
with literature review through
November 2018; no references added. Policy statement
unchanged.
04/01/20 Delete policy, approved March 10, 2020. This policy
will be deleted effective July 2,
2020, and replaced with InterQual criteria for dates of service
on or after July 2, 2020.
Approved March 19, 2020, policy updated with literature review
through November
2019; no references added. Policy statement unchanged. Removed
CPT code 38242
effective April 1, 2020; code does not match criteria.
-
Page | 24 of 24 ∞
Date Comments 06/10/20 Interim Review, approved June 9, 2020,
effective June 10, 2020. This policy is reinstated
immediately and will no longer be deleted or replaced with
InterQual criteria on July 2,
2020.
Disclaimer: This medical policy is a guide in evaluating the
medical necessity of a particular service or treatment. The
Company adopts policies after careful review of published
peer-reviewed scientific literature, national guidelines and
local standards of practice. Since medical technology is
constantly changing, the Company reserves the right to review
and update policies as appropriate. Member contracts differ in
their benefits. Always consult the member benefit
booklet or contact a member service representative to determine
coverage for a specific medical service or supply.
CPT codes, descriptions and materials are copyrighted by the
American Medical Association (AMA). ©2020 Premera
All Rights Reserved.
Scope: Medical policies are systematically developed guidelines
that serve as a resource for Company staff when
determining coverage for specific medical procedures, drugs or
devices. Coverage for medical services is subject to
the limits and conditions of the member benefit plan. Members
and their providers should consult the member
benefit booklet or contact a customer service representative to
determine whether there are any benefit limitations
applicable to this service or supply. This medical policy does
not apply to Medicare Advantage.
-
Discrimination is Against the Law
Premera Blue Cross complies with applicable Federal civil rights
laws and does not discriminate on the basis of race, color,
national origin, age, disability, or sex. Premera does not exclude
people or treat them differently because of race, color, national
origin, age, disability or sex.
Premera: • Provides free aids and services to people with
disabilities to communicate
effectively with us, such as: • Qualified sign language
interpreters • Written information in other formats (large print,
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electronic formats, other formats) • Provides free language
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You can also file a civil rights complaint with the U.S.
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Lakkoofsa bilbilaa 800-722-1471 (TTY: 800-842-5357) tii
bilbilaa.
Français (French): Cet avis a d'importantes informations. Cet
avis peut avoir d'importantes informations sur votre demande ou la
couverture par l'intermédiaire de Premera Blue Cross. Le présent
avis peut contenir des dates clés. Vous devrez peut-être prendre
des mesures par certains délais pour maintenir votre couverture de
santé ou d'aide avec les coûts. Vous avez le droit d'obtenir cette
information et de l’aide dans votre langue à aucun coût. Appelez le
800-722-1471 (TTY: 800-842-5357).
Kreyòl ayisyen (Creole): Avi sila a gen Enfòmasyon Enpòtan
ladann. Avi sila a kapab genyen enfòmasyon enpòtan konsènan
aplikasyon w lan oswa konsènan kouvèti asirans lan atravè Premera
Blue Cross. Kapab genyen dat ki enpòtan nan avi sila a. Ou ka gen
pou pran kèk aksyon avan sèten dat limit pou ka kenbe kouvèti
asirans sante w la oswa pou yo ka ede w avèk depans yo. Se dwa w
pou resevwa enfòmasyon sa a ak asistans nan lang ou pale a, san ou
pa gen pou peye pou sa. Rele nan 800-722-1471 (TTY:
800-842-5357).
Deutsche (German): Diese Benachrichtigung enthält wichtige
Informationen. Diese Benachrichtigung enthält unter Umständen
wichtige Informationen bezüglich Ihres Antrags auf
Krankenversicherungsschutz durch Premera Blue Cross. Suchen Sie
nach eventuellen wichtigen Terminen in dieser Benachrichtigung. Sie
könnten bis zu bestimmten Stichtagen handeln müssen, um Ihren
Krankenversicherungsschutz oder Hilfe mit den Kosten zu behalten.
Sie haben das Recht, kostenlose Hilfe und Informationen in Ihrer
Sprache zu erhalten. Rufen Sie an unter 800-722-1471 (TTY:
800-842-5357).
Hmoob (Hmong): Tsab ntawv tshaj xo no muaj cov ntshiab lus tseem
ceeb. Tej zaum tsab ntawv tshaj xo no muaj cov ntsiab lus tseem
ceeb txog koj daim ntawv thov kev pab los yog koj qhov kev pab cuam
los ntawm Premera Blue Cross. Tej zaum muaj cov hnub tseem ceeb uas
sau rau hauv daim ntawv no. Tej zaum koj kuj yuav tau ua qee yam
uas peb kom koj ua tsis pub dhau cov caij nyoog uas teev tseg rau
hauv daim ntawv no mas koj thiaj yuav tau txais kev pab cuam kho
mob los yog kev pab them tej nqi kho mob ntawd. Koj muaj cai kom
lawv muab cov ntshiab lus no uas tau muab sau ua koj hom lus pub
dawb rau koj. Hu rau 800-722-1471 (TTY: 800-842-5357).
Iloko (Ilocano): Daytoy a Pakdaar ket naglaon iti Napateg nga
Impormasion. Daytoy a pakdaar mabalin nga adda ket naglaon iti
napateg nga impormasion maipanggep iti apliksayonyo wenno coverage
babaen iti Premera Blue Cross. Daytoy ket mabalin dagiti importante
a petsa iti daytoy a pakdaar. Mabalin nga adda rumbeng nga
aramidenyo nga addang sakbay dagiti partikular a naituding nga
aldaw tapno mapagtalinaedyo ti coverage ti salun-atyo wenno tulong
kadagiti gastos. Adda karbenganyo a mangala iti daytoy nga
impormasion ken tulong iti bukodyo a pagsasao nga awan ti
bayadanyo. Tumawag iti numero nga 800-722-1471 (TTY:
800-842-5357).
Italiano ( ):Questo avviso contiene informazioni importanti.
Questo avviso può contenere informazioni importanti sulla tua
domanda o copertura attraverso Premera Blue Cross. Potrebbero
esserci date chiave in questo avviso. Potrebbe essere necessario un
tuo intervento entro una scadenza determinata per consentirti di
mantenere la tua copertura o sovvenzione. Hai il diritto di
ottenere queste informazioni e assistenza nella tua lingua
gratuitamente. Chiama 800-722-1471 (TTY: 800-842-5357).
Italian
中文 (Chinese):本通知有重要的訊息。本通知可能有關於您透過 Premera Blue Cross
提交的申請或保險的重要訊息。本通知內可能有重要日期。您可能需要在截止日期
之前採取行動,以保留您的健康保險或者費用補貼。您有權利免費以您的母
語得到本訊息和幫助。請撥電話 800-722-1471 (TTY: 800-842-5357)。
037338 (07-2016)
https://www.hhs.gov/ocr/office/file/index.htmlhttps://ocrportal.hhs.gov/ocr/portal/lobby.jsfmailto:[email protected]
-
日本語 (Japanese):この通知には重要な情報が含まれています。この通知には、 Premera Blue
Crossの申請または補償範囲に関する重要な情報が含まれている場合があります。この通知に記載されている可能性がある重要な日付をご確認くだ
さい。健康保険や有料サポートを維持するには、特定の期日までに行動を
取らなければならない場合があります。ご希望の言語による情報とサポー
トが無料で提供されます。800-722-1471 (TTY: 800-842-5357)までお電話ください。
한국어 (Korean): 본 통지서에는 중요한 정보가 들어 있습니다 . 즉 이 통지서는 귀하의 신청에 관하여 그리고
Premera Blue Cross 를 통한 커버리지에 관한 정보를 포함하고 있을 수 있습니다 . 본 통지서에는 핵심이
되는 날짜들이 있을 수 있습니다. 귀하는 귀하의 건강 커버리지를 계속 유지하거나 비용을 절감하기 위해서 일정한 마감일까지
조치를 취해야 할 필요가 있을 수 있습니다 . 귀하는 이러한 정보와 도움을 귀하의 언어로 비용 부담없이 얻을 수 있는
권리가 있습니다 . 800-722-1471 (TTY: 800-842-5357) 로 전화하십시오 .
ລາວ (Lao): ແຈ້ງການນີ້ ນສໍ າຄັນ. ແຈ້ງການນີ້ອາດຈະມີ ນສໍ
າຄັນກ່ຽວກັບຄໍ າຮ້ອງສະ ກ ຫຼື ຄວາມຄຸ້ມຄອງປະກັນໄພຂອງທ່ານຜ່ານ Premera
Blue Cross. ອາດຈະມີ ນທີ າຄັນໃນແຈ້ງການນີ້. ທ່ານອາດຈະຈໍ າເປັ ນຕ້ອງດໍ
າເນີ ນການຕາມກໍ ານົດ ເວລາສະເພາະເພື່ອຮັກສາຄວາມຄຸ້ມຄອງປະກັນສຸຂະພາບ ຫຼື
ຄວາມຊ່ວຍເຫຼື ອເລື່ອງ າໃຊ້ າຍຂອງທ່ານໄວ້ . ທ່ານມີ ດໄດ້ ບຂໍ້ ນນີ້ ແລະ
ຄວາມຊ່ວຍເຫຼື ອເປັ ນພາສາ ຂອງທ່ານໂດຍບ່ໍ ເສຍຄ່າ. ໃຫ້ໂທຫາ 800-722-1471
(TTY: 800-842-5357).
ູຂໍ້
່
ສໍ ັ
ຈ
ໝ
ສິ
ັ
່
ວ
ຄ
ມ
ມູຮັ
ູມີ ມຂໍ້
ភាសាែខមរ ( ): ឹ
រងរបស់
Premera Blue Cross ។ របែហលជាមាន កាលបរ ិ ឆ ំខានេនៅកងេសចក
េសចកតជី ូ
ជាមានព័ ៌ ៉ ងសំ ់អពី ់ ៉ ប់
នដំ ងេនះមានព័ ី
តមានយា ខាន ំ ទរមងែបបបទ ឬការរា
ណ ត៌មានយ៉ា ំ ់ តងសខាន។ េសចក
េចទស ់ ន ុ ត
ណងេនះ។ អ វការបេញញសមតភាព ដលកណតៃថ ចបាស
កតាមរយៈ
ដំ ឹ នករបែហលជារតូ ច ថ ់ ំ ់ ងជាក់ ់
នដ
ន
ី ន
ូ
អ
ូ
ជ
ជ
ំណឹងេនះរបែហល
នានា េដើ ីនងរកសាទុ ៉ បរងស់ ុ ់ ក ឬរបាក់ ំ
អ
មប ឹ កការធានារា ខភាពរបស ជ
ធនកមានសិ ទទលព័ មានេនះ និ ំ យេនៅកុងភាសារបសទិ ួ ត៌ ងជ ននួ
ន
់ កេដាយម
អ
នអ
យេចញៃថល។ ួ
នអស
ន
ិ
លុ ើ ូ ូយេឡយ។ សមទ ទ រស័ព 800-722-1471 (TTY: 800-842-5357)។
Khmer
ਕਵਰਜ ਅਤ ਅਰਜੀ ਬਾਰ ਮਹ ਤਵਪਰਨ ਜਾਣਕਾਰੀ ਹ ਸਕਦੀ ਹ . ਇਸ ਨ ਿਜਸ ਜਵਚ
ਖਾਸ
ਤਾਰੀਖਾ ਹ ਸਕਦੀਆ ਹਨ. ਜੇਕਰ ਤਸੀ ਜਸਹਤ ਕਵਰਜ ਿਰਖਣੀ ਹਵ ਜਾ ਓਸ ਦੀ ਲਾਗਤ
ਜਿਵਚ ਮਦਦ ਦ ੇਇਛ ੁਕ ਹ ਤਾਂ ਤਹਾਨ ਅ ਤਮ ਤਾਰੀਖ਼ ਤ ਪਿਹਲਾਂ ਕੁ ਝ ਖਾਸ ਕਦਮ ਚ ਕਣ
ਦੀ ਲੜ ਹ ਸਕਦੀ ਹ ,ਤਹੁਾਨ ਮਫ਼ਤ ਿਵਚ ਤ ਆਪਣੀ ਭਾਸ਼ਾ ਿਵ ਚ ਜਾਣਕਾਰੀ ਅਤ ਮਦਦ ਪਾਪਤ
ਕਰਨ ਦਾ ਅਿਧਕਾਰ ਹ ,ਕਾਲ 800-722-1471 (TTY: 800-842-5357).
ਪ ਜਾਬੀ (Punjabi): ਇਸ ਨ ਿਟਸ ਿਵਚ ਖਾਸ ਜਾਣਕਾਰੀ ਹ. ਇਸ ਨ ਿਟਸ ਿਵਚ
Premera Blue Cross ਵਲ ਤੁਹਾਡੀ
ੰ
ੰ
ੇ ੇ ੇ ੱ ੂ ੋ ੈ ੋੋ ਂ ੁ ੇ ੱ ੋ ੇ ੱੱ ੁ ੱ ੂੁ ੱ ੇ ੱ ੇ ੍ਰ ੈ
ੋ ੰ ੂ ੱ ੁ ੋ ੋ ੈ ੰ
ੋ ੈ ੋ
(Farsi): فارسی فرم بارهدر ھمم اطالعات حاوی است ممکن يهمالعا اين.
ميباشد ھمم اطالعات یوحا يهمالعا اين
در ھمم ھای خيتار به باشد.پ رایبستاکنممماش زينهھ اختدپر در مککيا
تان بيمهوشش حقظ
Premera Blue Cross طريق از ماش مهبيوشش يا و تقاضا ای پ. يدماين
جهتو يهمالعا اين
حق شما. يدشاب داشته اجتياح صیاخ کارھای امانج برای صیمشخ ایھ
خيتار به تان، انیمدر ھای کسب برای .نماييد دريافت گانيرا ورط به ودخ
زبان به را کمک و اطالعات اين که داريد را اين
استم ) 5357-842-800 مارهباش ماست TTY انکاربر(800-722-1471 مارهش
با اطالعات .اييدنم برقرار
้
Polskie (Polish): To ogłoszenie może zawierać ważne informacje.
To ogłoszenie może
zawierać ważne informacje odnośnie Państwa wniosku lub zakresu
świadczeń poprzez Premera Blue Cross. Prosimy zwrócic uwagę na
kluczowe daty, które mogą być zawarte w tym ogłoszeniu aby nie
przekroczyć terminów w przypadku utrzymania polisy ubezpieczeniowej
lub pomocy związanej z kosztami. Macie Państwo prawo do bezpłatnej
informacji we własnym języku. Zadzwońcie pod 800-722-1471 (TTY:
800-842-5357).
Português (Portuguese): Este aviso contém informações
importantes. Este aviso poderá conter informações importantes a
respeito de sua aplicação ou cobertura por meio do Premera Blue
Cross. Poderão existir datas importantes neste aviso. Talvez seja
necessário que você tome providências dentro de determinados prazos
para manter sua cobertura de saúde ou ajuda de custos. Você tem o
direito de obter e sta informação e ajuda em seu idioma e sem
custos. Ligue para 800-722-1471 (TTY: 800-842-5357).
Română (Romanian): Prezenta notificare conține informații
importante. Această notificare poate conține informații importante
privind cererea sau acoperirea asigurării dumneavoastre de sănătate
prin Premera Blue Cross. Pot exista date cheie în această
notificare. Este posibil să fie nevoie să acționați până la anumite
termene limită pentru a vă menține acoperirea asigurării de
sănătate sau asistența privitoare la costuri. Aveți dreptul de a
obține gratuit aceste informații și ajutor în limba dumneavoastră.
Sunați la 800-722-1471 (TTY: 800-842-5357).
Pусский (Russian): Настоящее уведомление содержит важную
информацию. Это уведомление может содержать важную информацию о
вашем заявлении или страховом покрытии через Premera Blue Cross. В
настоящем уведомлении могут быть указаны ключевые даты. Вам,
возможно, потребуется принять меры к определенным предельным срокам
для сохранения страхового покрытия или помощи с расходами. Вы
имеете право на бесплатное получение этой информации и помощь на
вашем языке. Звоните по телефону 800-722-1471 (TTY:
800-842-5357).
Fa’asamoa (Samoan): Atonu ua iai i lenei fa’asilasilaga ni
fa’amatalaga e sili ona taua e tatau ona e malamalama i ai. O lenei
fa’asilasilaga o se fesoasoani e fa’amatala atili i ai i le tulaga
o le polokalame, Premera Blue Cross, ua e tau fia maua atu i ai.
Fa’amolemole, ia e iloilo fa’alelei i aso fa’apitoa olo’o iai i
lenei fa’asilasilaga taua. Masalo o le’a iai ni feau e tatau ona e
faia ao le’i aulia le aso ua ta’ua i lenei fa’asilasilaga ina ia e
iai pea ma maua fesoasoani mai ai i le polokalame a le Malo olo’o e
iai i ai. Olo’o iai iate oe le aia tatau e maua atu i lenei
fa’asilasilaga ma lenei fa’matalaga i legagana e te malamalama i ai
aunoa ma se togiga tupe. Vili atu i le telefoni 800-722-1471 (TTY:
800-842-5357).
Español ( ): Este Aviso contiene información importante. Es
posible que este aviso contenga información importante acerca de su
solicitud o cobertura a través de Premera Blue Cross. Es posible
que haya fechas clave en este
tiene derecho a recibir esta información y ayuda en su idioma
sin costo
aviso. Es posible que deba tomar alguna medida antes de
determinadas fechas para mantener su cobertura médica o ayuda con
los costos. Usted
alguno. Llame al 800-722-1471 (TTY: 800-842-5357).
Spanish
Tagalog (Tagalog): Ang Paunawa na ito ay naglalaman ng
mahalagang impormasyon. Ang paunawa na ito ay maaaring naglalaman
ng mahalagang impormasyon tungkol sa iyong aplikasyon o pagsakop sa
pamamagitan ng Premera Blue Cross. Maaaring may mga mahalagang
petsa dito sa paunawa. Maaring mangailangan ka na magsagawa ng
hakbang sa ilang mga itinakdang panahon upang mapanatili ang iyong
pagsakop sa kalusugan o tulong na walang gastos. May karapatan ka
na makakuha ng ganitong impormasyon at tulong sa iyong wika ng
walang gastos. Tumawag sa 800-722-1471 (TTY: 800-842-5357).
ไทย (Thai): ประกาศนมขอมลสาคญ
ประกาศนอาจมขอมลทสาคญเกยวกบการการสมครหรอขอบเขตประกน สขภาพของคณผาน
Premera Blue Cross และอาจมกาหนดการในประกาศน คณอาจจะตอง
ดาเนนการภายในกาหนดระยะเวลาทแนนอนเพอจะรกษาการประกนสขภาพของคณหรอการชวยเหลอท
มคาใชจาย คณมสทธทจะไดรบขอมลและความชวยเหลอนในภาษาของคณโดยไม่มคาใชจาย
โทร 800-722-1471 (TTY: 800-842-5357)
้ี ี ้ ู ํ ั ้ี ี ้ ู ่ี ํ ั ่ี ั ั ื ัุ ุ ่ ี ํ ี ุ ้ํ ิ ํ ่ี ่
่ื ั ั ุ ุ ื ่ ื ่ีี ่ ้ ่ ุ ี ิ ิ ่ี ้ ั ้ ู ่ ื ้ี ุ ี ่ ้ ่
Український (Ukrainian): Це повідомлення містить важливу
інформацію. Це повідомлення може містити важливу інформацію про
Ваше звернення щодо страхувального покриття через Premera Blue
Cross. Зверніть увагу на ключові дати, які можуть бути вказані у
цьому повідомленні. Існує імовірність того, що Вам треба буде
здійснити певні кроки у конкретні кінцеві строки для того, щоб
зберегти Ваше медичне страхування або отримати фінансову допомогу.
У Вас є право на отримання цієї інформації та допомоги безкоштовно
на Вашій рідній мові. Дзвоніть за номером телефону 800-722-1471
(TTY: 800-842-5357).
Tiếng Việt (Vietnamese): Thông báo này cung cấp thông tin quan
trọng. Thông báo này có thông tin quan trọng về đơn xin tham gia
hoặc hợp đồng bảo hiểm của quý vị qua chương trình Premera Blue
Cross. Xin xem ngày quan trọng trong thông báo này. Quý vị có thể
phải thực hiện theo thông báo đúng trong thời hạn để duy trì bảo
hiểm sức khỏe hoặc được trợ giúp thêm về chi phí. Quý vị có quyền
được biết thông tin này và được trợ giúp bằng ngôn ngữ của mình
miễn phí. Xin gọi số 800-722-1471 (TTY: 800-842-5357).